Activation of MAT2A-ACSL3 pathway protects cells from ferroptosis in gastric cancer.
Free Radic Biol Med
; 181: 288-299, 2022 03.
Article
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| MEDLINE
| ID: mdl-35182729
ABSTRACT
BACKGROUND:
Ferroptosis, a unique form of nonapoptotic-regulated cell death caused by overwhelming lipid peroxidation, represents an emerging tumor suppression mechanism. Growing evidence has demonstrated that cell metabolism plays an important role in the regulation of ferroptosis. Specifically, the association between methionine metabolism and ferroptosis remains undefined.METHODS:
We performed in vitro and in vivo experiments to evaluate the influence of methionine metabolism on ferroptosis sensitivity. Pharmacological and genetic blockade of the methionine cycle was utilized and relevant molecular analyses were performed.RESULTS:
We identified MAT2A as a driver of ferroptosis resistance. Mechanistically, MAT2A mediates the production of S-adenosylmethionine (SAM), which upregulates ACSL3 by increasing the trimethylation of lysine-4 on histone H3 (H3K4me3) at the promoter area, resulting in ferroptosis resistance.CONCLUSIONS:
Collectively, these results established a link between methionine cycle activity and ferroptosis vulnerability in gastric cancer.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
/
Coenzima A Ligasas
/
Ferroptosis
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Metionina Adenosiltransferasa
Límite:
Humans
Idioma:
En
Revista:
Free Radic Biol Med
Asunto de la revista:
BIOQUIMICA
/
MEDICINA
Año:
2022
Tipo del documento:
Article